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Inhibiting the Nrf2/HO-1 signaling cascade weakens the pro-inflammatory response induced by gasoline engine exhaust in lung epithelial cells following air-liquid interface exposure.

Inhalation toxicology 2026 p. 1-15 Genomics, phytochemicals, and oxidat
OpenAlex 토픽 · Genomics, phytochemicals, and oxidative stress Advanced Glycation End Products research Air Quality and Health Impacts

Qu Y, Li G, Yu T, Zhang X, Zhao W, Zheng M, Li B, Bin P

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[OBJECTIVE] This study aimed to investigate the role of the nuclear factor erythroid 2-related factor 2/heme oxygenase-1 (Nrf2/HO-1) signaling cascade in the inflammatory responses induced by whole ga

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APA Ying Qu, G Li, et al. (2026). Inhibiting the Nrf2/HO-1 signaling cascade weakens the pro-inflammatory response induced by gasoline engine exhaust in lung epithelial cells following air-liquid interface exposure.. Inhalation toxicology, 1-15. https://doi.org/10.1080/08958378.2026.2659193
MLA Ying Qu, et al.. "Inhibiting the Nrf2/HO-1 signaling cascade weakens the pro-inflammatory response induced by gasoline engine exhaust in lung epithelial cells following air-liquid interface exposure.." Inhalation toxicology, 2026, pp. 1-15.
PMID 42011764

Abstract

[OBJECTIVE] This study aimed to investigate the role of the nuclear factor erythroid 2-related factor 2/heme oxygenase-1 (Nrf2/HO-1) signaling cascade in the inflammatory responses induced by whole gasoline engine exhaust (GEE) in lung epithelial cells air-liquid interface (ALI) exposure.

[MATERIALS AND METHODS] Using an ALI exposure system, human bronchial epithelial cells (BEAS-2B) and type II alveolar epithelial cells (A549) were exposed to whole GEE collected from a two-wheeled motorcycle at various dilution ratios. After a 1 h exposure at 10 mL/min, cell relative viability, intracellular reactive oxygen species (ROS), glutathione (GSH), oxidized glutathione (GSSG) and the GSH/GSSG ratio were measured. Inflammatory cytokines (IL-1β, IL-6, and IL-8) were quantified. The Nrf2 inhibitor brusatol (BR, 300 nM) and the antioxidant N-acetyl-L-cysteine (NAC, 5 mM) were used to modulate the Nrf2/HO-1 pathway and oxidative stress, respectively. Protein and gene expression levels were analyzed by Western Blotting and real-time PCR.

[RESULTS] Exposure to 10%GEE induced oxidative stress and optimally activated Nrf2/HO-1 expression without cytotoxicity, while higher concentrations suppressed this signaling pathway. Significant correlations were observed between Nrf2/HO-1 levels and inflammatory cytokines. Inhibition of Nrf2/HO-1 with BR reduced inflammatory responses which induced by the 10%GEE in both BEAS-2B and A549 cell lines. Furthermore, attenuating oxidative stress with NAC inhibited both Nrf2/HO-1 expression and the GEE-induced inflammatory response.

[CONCLUSION] Inhibiting the Nrf2/HO-1 signaling cascade attenuates the pro-inflammatory response induced by GEE in lung epithelial cells following ALI exposure. The Nrf2/HO-1 pathway appears to be a critical regulator of GEE-induced pulmonary inflammation, highlighting its potential as a therapeutic target.

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